Optimization of the LC enantioseparation of chiral pharmaceuticals using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral selector and polar non-aqueous mobile phases

The resolving power of a new commercial polysaccharide-based chiral stationary phase,
Sepapak-4, with cellulose tris(4-chloro-3-methylphenylcarbamate) coated on silica microparticles as chiral selector, was evaluated toward the enantioseparation of ten basic drugs
with widely different structures and hydrophobic properties, using ACN as the main
component of the mobile phase. A multivariate approach (experimental design) was used
to screen the factors (temperature, n-hexane content, acidic and basic additives) likely to
influence enantioresolution. Then, the optimization was performed using a face-centered
central composite design. Complete enantioseparation could be obtained for almost all
tested chiral compounds, demonstrating the high chiral discrimination ability of this
chiral stationary phase using polar organic mobile phases made up of ACN and
containing an acidic additive (TFA or formic acid), 0.1% diethylamine and n-hexane.
These results clearly illustrate the key role of the nature of the acidic additive in the mobile
phase.